The Age-Related Eye Disease Study (AREDS) is a large multicenter study of the natural course and clinical prognosis of age-related cataract and age-related macular degeneration (AMD). Observational and experimental data suggest that antioxidant and/or zinc supplements may delay progression of age-related cataract, age-related macular degeneration (AMD) and vision loss. The study also evaluated the effect of high-dose vitamins C and E, beta carotene, and zinc supplements on cataract and AMD progression and visual acuity. The study enrolled participants in an AMD trial if they had extensive small drusen, intermediate drusen, large drusen, noncentral geographic atrophy, or pigment abnormalities in 1 or both eyes, or advanced AMD or vision loss due to AMD in 1 eye. At least 1 eye had best-corrected visual acuity of 20/32 or better. Participants were randomly assigned to receive daily oral tablets containing: (1) antioxidants (vitamin C, 500 mg; vitamin E, 400 IU; and beta carotene, 15 mg); (2) zinc, 80 mg, as zinc oxide and copper, 2 mg, as cupric oxide; (3) antioxidants plus zinc; or (4) placebo. The main outcomes of interest were: (1)Photographic assessment of progression of lens opacities and also of progression to or treatment for advancedAMD and (2) at least moderate visual acuity loss from baseline (more than 15 letters). Serum level measurements, medical histories, and mortality rates were used for safety monitoring. In the last year, the results of the study were announced after an average follow-up of the 4757 enrolled study participants of 6.3 years. No beneficial effect was found for preventing the progression of lens opacities or cataract surgery. Participants with extensive small drusen, nonextensive intermediate size drusen, or pigment abnormalities had only a 1.3% 5-year probability of progression to advanced AMD. The results were then limited to those with intermediate drusen, large drusen or more severe AMD findings. Comparison with placebo demonstrated a statistically significant reduction for the development of advanced AMD with antioxidants plus zinc by as much as 25% (p<.01). Treatment with zinc alone also reduced this risk by 19% (p<.01). The only statistically significant reduction of 19%in rates of at least moderate visual acuity loss occurred in persons assigned to receive antioxidants plus zinc (p < 0.01). No statistically significant serious adverse effect was associated with any of the formulations. Beta carotene increased yellowing of the skin and zinc increased hospitalizations for genitourinary problems in men. Persons older than 55 years should have dilated eye examinations to determine their risk of developing advanced AMD. Those with extensive intermediate size drusen, at least 1 large druse, noncentral geographic atrophy in 1 or both eyes, or advanced AMD or vision loss due to AMD in 1 eye, and without contraindications such as smoking, should consider taking a supplement of antioxidants plus zinc such as that used in this study. The Age-Related Eye Disease study will complete follow-up of study participants in 2005 and will continue to prepare a series of manuscripts summarizing study results.